Kari Almendingen

Growth and recurrence of colorectal polyps: a double-blind 3-year intervention with calcium and antioxidants.

Background: Dietary calcium and antioxidants have been suggested as protective agents against colorectal cancer. This has been supported by animal experimental studies, case control and cohort studies. Materials and Methods: In a prospective intervention study of colorectal adenomas, and intermediary stage in colorectal carcinogenesis, 116 polyp-bearing patients received a placebo-controlled daily mixture of β-carotene 15 mg, vitamin C 150 mg, vitamin E 75 mg, selenium 101 µg, and calcium (1.6 g daily) as carbonate for a period of 3 years with annual colonoscopic follow-up to test if the mixture was able to reduce polyp growth or recurrence. All polyps of <10 mm at enrolment or follow-up were left unresected until the end of the study. Results: 87–91% of the patients attended the annual endoscopic follow-up investigations, and 19% of the patients dropped out of the medical intervention. The rest consumed 85% of the total amount of tablets over the 3 years. The fecal calcium concentration was 2.3–2.7 times higher in patients taking active medication compared to the placebo group. Diet registration showed that, when adding the intake of antioxidants and calcium from diet and intervention, there was a significant difference between the intake of these substances in the active and the placebo group. No difference was detected in the growth of adenomas between the active and the placebo group from year to year and for the total study period. Moreover, there was no effect on polyps of <5 or 5–9 mm, or on polyps in the different colonic segments analyzed separately. A reduced growth of adenomas was found in patients <60 years of age taking active medication (n = 8) compared to those taking placebo (n = 6; mean difference 2.3 mm; 95% CI 0.26–4.36). There was a significantly lower number of patients free of new adenomas in the placebo group compared to those taking active medication as tested by logistic regression and Kaplan-Meier analysis (log-rank test p value 0.035). Subgroup analysis showed that only the group of patients with no family history of colorectal cancer, those with only one adenoma at inclusion, and those <65 years benefitted from the intervention medication. Conclusion: The study did not find an overall effect on polyp growth. Our data, however, may support a protective role of calcium and antioxidants on new adenoma formation.

Adipose tissue fatty acids and risk of myocardial infarction--a case-control study.

Objectives: To study the association between content in adipose tissue of very long-chain n-3 fatty acids, trans fatty acids, linoleic acid and α-linolenic acid and risk of a first myocardial infarction.Design and subjects: A case-control design among 100 patients and 98 population controls both men and postmenopausal women, age 45–75 y. Adipose tissue fatty acids were determined by gas–liquid chromatography. Intake data were obtained through interview using a validated food frequency questionnaire.Results: Dietary intake and adipose tissue content of the fatty acids studied correlated significantly. Adipose tissue contents of eicosapentaenoic acid (20:5n-3), docosapentaenoic acid (22:5n-3) and docosahexaenoic acid (22:6n-3) were significantly lower while those of trans fatty acids, linoleic and α-linolenic acid were significantly higher in patients than in controls. Age and sex adjusted odds ratios (OR) were significantly reduced with increasing quintiles of very long-chain n-3 fatty acids, thus the OR in the fifth compared to the first quintile was 0.23 (95% CI 0.08–0.70). After further adjustment for waist-to-hip ratio, smoking, family history of CHD and content of trans fatty acids, the OR in the highest quintile was 0.17 (95% CI 0.04–0.76) and the P for trend 0.016. Age and sex adjusted OR was increased in the fifth compared to the first quintile of trans fatty acids (OR 2.81, 95% CI 1.16–6.84), linoleic acid (OR 2.10, 95% CI 0.87–5.07) and α-linolenic acid (OR 1.96, 95% CI 0.83–4.61), and P for trend was 0.002, 0.005 and 0.020, respectively. The trends remained significant after adjustment for waist-to-hip ratio, smoking, and family history of coronary heart disease. Trans fatty acids, linoleic acid and α-linolenic acid in adipose tissue were strongly correlated, indicating a common source, most likely margarine. When each of these fatty acid species were adjusted for the two others the trends were no longer significant.Conclusion: Intake of very long-chain n-3 fatty acids as reflected in adipose tissue content is inversely associated with risk of myocardial infarction. Trans fatty acids, linoleic and α-linolenic acid were intercorrelated and associated with increased risk. It is suggested that the increased risk may be connected to trans fatty acids or to some other factor associated with margarine consumption.Sponsorship: Throne Holsts Foundation for Nutrition Research, The Norwegian Association of Margarine Producers, DeNoFa Fabriker A/S, Tine Norwegian Dairies.European Journal of Clinical Nutrition 54, 618–625.

Does high body fatness increase the risk of presence and growth of colorectal adenomas followed up in situ for 3 years

OBJECTIVE:Obesity is an increasing problem for industrialized nations. The incidence of colorectal cancer has also risen during the last decades. However, information is scarce about the association between the colorectal cancer precursors, adenomatous polyps, and body composition. Our aim was to find out if body fatness is related to the presence of polyps and of growth of adenomas of ≤9 mm observed in situ over 3 yr.METHODS:Twenty-eight outpatients with colorectal polyps and 50–75 yr of age were compared with 34 sex- and age-matched (±5 yr) polyp-free healthy controls. The polyp patients were randomly selected from a double blind 3-yr placebo-controlled endoscopic follow-up and intervention study against growth and recurrence of polyps among 116 polyp-bearing outpatients. Triceps skinfold thickness (TSF) was measured by a Harpenden caliper and total body fat percentage (BF%) by Futrex 5000. Dietary intake was calculated in a 5-day dietary record by weighing. Demograpic data, including smoking and alcohol habits, were registered by an interview and self-administrated questionnaires. Weight and height were measured.RESULTS:TSF and BF% ranked 66% of the individuals into the same quartiles, and 34% were ranked into the adjacent quartiles. The coefficient of correlation between TSF and BF% was highly significant (r = 0.90, p < 0.01, n = 62). TSF, BF%, and body mass index (kg/m2) did not differ between polyp patients and controls in either crude or adjusted analyses. Adenoma growth was, however, highly associated with increasing levels of TSF (p = 0.004), BF% (p = 0.02), and body mass index (p = 0.006).CONCLUSIONS:Our data suggest that high body fatness is a promoter of adenoma growth. Similar results were obtained with the caliper and Futrex 5000, which lends credibility to this study. For repeated documentation, a larger study population should be investigated. To our knowledge, this is the first case-control study to investigate the relationship between body composition and growth of adenoma by follow-up in situ over 3 yr.

Lifestyle as a predictor for colonic neoplasia in asymptomatic individuals

BackgroundLifestyle is a well-established risk factor for colorectal cancer (CRC) and is also found to be associated with occurrence of adenomas. In the present study we evaluated risk factors for both low-risk adenomas and advanced neoplasia in asymptomatic individuals using a single-paged questionnaire. Aiming to see if the questionnaire was a useful tool in picking up high-risk individuals.MethodsA cross-sectional study was carried out within a randomised controlled colorectal cancer screening trial (n = 6961). The population comprised men and women born between 1946 and 1950. Before screening in year 2001 they were asked to fill in a questionnaire about their present lifestyle. Cases were categorised according to the most severe findings at screening. Analyses were then conducted to find risk factors associated with the presence of either low-risk adenomas or advanced neoplasia.ResultsThe response rate among attendees was 97% (3998/4111). Among these, 3447 (86%) had no neoplasia, 443 (11%) had low-risk adenomas, and 108 (3%) had advanced neoplasia. Low-risk adenomas were significantly associated with current smoking, and obesity. Participants with advanced neoplasia had a two-fold increased risk of not adhering to any of the selected lifestyle recommendations compared to controls. However, current smoking was the only variable that reached statistical significance in the multivariate analysis for these lesions. A dose-response relationship to the consumption of cigarettes per day was shown, where OR was 2.04 (CI 1.07–3.89) for the lowest consumption category.ConclusionThe present findings indicate that a short questionnaire may be adequate in picking up the most consistent associations between lifestyle risk factors and colorectal neoplasia. Smoking and BMI were found to be the most significant risk factors for neoplasia, but adhering to recommendations on diet, and physical activity seems also to be of importance.

Smoking and colorectal adenomas: a case-control study.

The short-chain fatty acid butyrate is regarded as a regulative agent in haemostasis of mucosal cell turnover. Inhibition of prostaglandin E2 synthesis is particularly involved in this regulation process. In the present study, proliferation was stimulated in colonic biopsies of 12 healthy subjects (age 51.3 years, range 25-81) by incubation with deoxycholic acid (5 micromol/l DCA). The anti-proliferative and cyclo-oxygenase-inhibiting properties of butyrate (10 mmol/l BUT) and of aspirin (555 micromol/l ASA) were investigated. Colonic cell proliferation was determined by bromodeoxyuridine immunohistochemistry. PGE2 release into the incubation medium was measured by radioimmunoassay. Incubation with DCA/ASA, DCA/BUT and DCA/ASA/BUT revealed a significant reduction in crypt cell proliferation as measured by the labelling index of the whole crypt in comparison to incubation with DCA alone (DCA/ASA: 0.14, P < 0.01; DCA/BUT: 0.15, P < 0.05; DCA/ASA/BUT: 0.15, P < 0.05, versus DCA: 0.18). The labelling index for the upper 40% of the crypt was only lower after incubation with DCA/ASA (0.023) compared to DCA (0.028) (P < 0.05). PGE2 release from biopsy specimens was only significantly decreased in the incubation media where ASA was added (DCA/ASA: 29.0 pg/mg mucosa/h, P < 0.005; DCA/ASA/BUT: 31.4 pg/mg mucosa/h, P < 0.01 versus DCA: 56.9 pg/mg mucosa/h). Butyrate and aspirin showed no synergistic effects. The results indicate a normalization of DCA-induced hyperproliferation of colonic mucosa by butyrate, and, even more efficiently, by aspirin. The data support the hypothesis that butyrate and aspirin can act as chemopreventive agents in colon carcinogenesis.

Effects of Partially Hydrogenated Fish Oil, Partially Hydrogenated Soybean Oil, and Butter on Hemostatic Variables in Men

We have compared the effects of partially hydrogenated fish oil (PHFO diet), partially hydrogenated soybean oil (PHSO diet), and butterfat (butter diet) on fibrinolytic and coagulation variables in 31 young men. The three test margarines, which contributed 78% of total fat in the diets, contained 70% butterfat, PHSO, or PHFO, each with 30% of soybean oil. Fat provided approximately 35% of energy, and the content of trans-fatty acids was 0.9%, 8.5%, and 8.0% of energy in the butter diet, PHSO diet, and PHFO diet, respectively. All diets contained 420 mg cholesterol per 10 megajoules per day. All subjects consumed all three test diets for 3 weeks, in a random order (crossover design). The PHSO diet resulted in higher levels of plasminogen activator inhibitor type 1 antigen and plasminogen activator inhibitor type 1 activity than the two other test diets. Fibrinogen increased on the butter diet compared with the PHFO diet. No significant differences in the levels of factor VII, fibrinopeptide A, D-dimer, tissue plasminogen activator or beta-thromboglobulin were observed between the three test diets. The PHFO and the PHSO diets have previously been shown to result in higher levels of Lp(a) compared with the butter diet. The present findings indicate that PHSO has unfavorable antifibrinolytic effects relative to PHFO and butter and that butter may be procoagulant relative to PHFO. More controlled studies are needed to assess definitely the impact of different hydrogenated fats on risk of coronary heart disease.

An assessment of the use of simple methods to predict individual energy intakes for intervention studies

Objective: To investigate to what extent individual energy intakes can be predicted by rapid easily available low-cost estimation methods.Design: Data were obtained from a controlled dietary intervention study period of nine weeks in which the subjects should be weight stable.Subjects: Thirty-one male students in domestic and kitchen management aged 29±6 y.Methods: (1) energy intake calculated from a quantitative food frequency questionnaire (FFQEI); (2) energy expenditure derived from estimates of basal metabolic rate (BMR) (FAO/WHO/UNU, 1985) based on weight, gender, age and low (1.55×BMR), medium (1.78×BMR) or high (2.10×BMR) level of activity. Level of activity was determined by questions concerning habitual activities lasting more than 20 min (WHOEE); (3) energy expenditure derived from individual recording in a specially prepared activity diary (ADEE). During the intervention, the subjects were to be fed test diets which should provide them with enough energy to keep them weight stable. The energy levels were established after taking both the FFQEIs, WHOEEs and ADEEs into consideration, and 10 MJ, 13 MJ, 15 MJ and 17 MJ per day were chosen because these levels were estimated to closely match the energy requirements of most of the subjects. The levels of energy were changed during the intervention period if the weight of the subjects fluctuated. The served level of energy at the last day of the intervention was denoted the weight maintenance energy intake (WMEI). WMEI was compared to FFQEI, WHOEE and ADEE in order to evaluate if one estimation method predicted WMEI better than the two others.Results: None of the three methods provided accurate estimates of WMEI of 13.3±1.8 MJ. However, WHOEE, gave the best estimate as demonstrated by the limits of agreement: −8.7 MJ to +8.9 MJ for FFQEI, −5.4 MJ to +3.9 MJ for WHOEE and −7.2 MJ to +5.2 MJ for ADEE. The coefficients of correlation between the differences and the means of WMEI and FFQEI, WHOEE and ADEE were −0.8 (P≤0.001), 0.1 (P=0.6, NS) and −0.5 (P≤0.01), respectively. The coefficients of variation were 34.6% for FFQEI, 11.3% for WHOEE, and 21.0% for ADEE.Conclusions: Although not precise, WHOEE showed the best agreement with the WMEI. These results demonstrate that a rapid and simple low-cost method predicted WMEI closely enough to avoid major weight fluctuations among these men during the intervention period.Sponsorship: Supported by The Research Society of the Norwegian Edible Fat Producers and the food company Mills DA, Oslo, Norway.

Does a family history of cancer increase the risk of occurrence, growth, and recurrence of colorectal adenomas?

Background: Familial history of colorectal cancer (FHCRC) is a recognised risk factor for sporadic CRC. The relationship to the growth rate of adenomas is largely unknown. Lifestyle related factors, which may also cluster in families, are also recognised risk factors for adenomas and CRC. Aims: To study the relationships between FHCRC and family history of other cancers (FHOC) among first degree relatives in relation to occurrence, growth, and recurrence of adenomas. Patients and methods: Eighty seven patients with adenomas, participating in a double blind, three year, placebo controlled, endoscopic follow up and intervention study of growth and recurrence of polyps (50% men, 50–76 years). Polyps >9 mm were removed whereas the remainder and newly discovered polyps <10 mm were left in situ for three years before removal and histological diagnosis. Data were collected by means of dietary records, interviews, and questionnaires. Results: The adenoma cases with FHCRC had a fourfold higher risk of adenoma growth. In contrast, no significant association was found for adenoma recurrence. FHOC was not significantly related to increased risk of growth or recurrence. Family history showed no significant association with the risk of baseline adenoma occurrence. Adjustment for CRC risk factors, also known to cluster in families, did not alter the results. Conclusions: FHCRC seems to be a strong risk factor for adenoma growth, but not for the earlier phases of CRC development such as the initiation of adenomas.

Current diet and colorectal adenomas: a case-control study including different sets of traditionally chosen control groups.

High intake of fat and a low intake of foods rich in antioxidants and fibre are suggested to be associated with risk of colorectal adenomas. Inconsistency may, however, be due to dietary assessment problems or differences in the identification of cases and controls. We have compared 87 adenoma cases aged 50–76 years with 35 healthy controls and 35 ‘hospital’ controls. All the controls were matched for sex and age (±5 years) and proven to be free of polyps. Current habitual diet was measured by a 5‐day dietary record by weighing. Regarding the intakes of vegetable fat, protein, cholesterol, vitamin A, total vitamin D, edible fats, coffee and fish and fish products, the outcomes of the analysis depended upon the source of controls. However, an increased adenoma risk compared with either set of controls related to a low consumption of vegetables, cereals, iron, vitamin C and fibre and a high intake of total fat was found. This is suggestive of substantial differences, since bias due to abdominal symptoms, the dietary records or an inappropriate choice of controls, would have affected the estimations. The findings give further strength to the role of these dietary factors in the formation of precancerous lesions in the large intestine.

Dietary habits and growth and recurrence of colorectal adenomas: Results from a three-year endoscopic follow-up study

Abstract: Diet has been associated with sporadic colorectal cancer (CRC) risk. The relationship to the growth rate of adenomas is largely unknown. Previous analyses of our cohort of polyp cases have shown 1) indicators of a healthy diet were inversely associated with adenoma occurrence, 2) diet was related to the fecal profile, 3) obesity was positively associated with adenoma growth, 4) familial predisposition of CRC was positively associated with adenoma growth, and 5) intervention with calcium and antioxidants was not associated with adenoma growth. The present aim was to study the effects of diet on growth and recurrence of adenomas. Data were collected from a 3-yr polyp growth and intervention study. Polyps larger than 9 mm were removed, whereas the remainder and newly discovered polyps smaller than 10 mm were left in situ for 3 yr. Diet was assessed by a 5-day dietary record by weighing (DR) and food-frequency questionnaire (FFQ). Weak inverse associations were found only between adenoma growth and fruits and berries (adjusted odds ratio, aOR = 0.3; 95% CI = 0.1-0.9) and carbohydrates (aOR = 0.1; 95% CI = 0.1-0.6; both only DR data) and between adenoma recurrence and vegetables (crude odds ratio, cOR = 0.4; 95% CI = 0.1-0.9; only FFQ data). Taken together, the present and previous findings from this cohort may indicate an early role for dietary factors in CRC development.